Abstract The pervasive contamination of drinking water resources by toxic per- and polyfluorinated alkyl substances (PFASs), such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), has emerged as a major health crisis affecting millions of people across the U.S. Given the environmental persistence of these contaminants and their established linkage to serious health risks, it is imperative that safe, efficient, and cost- effective PFAS remediation technologies be developed that can eliminate these contaminants from the U.S. water supplies. While PFOA and PFOS have been the two of the most widely studied PFASs, twelve other PFASs have also been measured in the blood serum of Americans over the age of twelve. Currently, the U.S. Environmental Protection Agency has a non-enforceable Lifetime Health Advisory guideline of 70 parts per trillion (ppt), which applies only to the combination of PFOA and PFOS. However, faced with growing pressure to address PFAS contamination, numerous States have acted to address the PFAS crisis, proposing limits as low as 10 ppt of individual PFASs and for a broader class of PFASs. Although different technologies have been explored for remediation of PFAS-contaminated water, adsorption-based methods using activated carbon or ion- exchange resins remain the most widely used approach. These adsorbents also have well-demonstrated shortcomings such as significant fouling by natural organic matter and/or other water matrix constituents and energy-intensive or difficult regeneration process that limits their reusability and lifetime. CycloPure is developing a novel class of cyclodextrin-based polymer adsorbents with high affinity for PFASs in order to address the urgent need for a highly-scalable, cost-effective method to eliminate PFASs from drinking water supplies. During the Phase I period, a promising approach was identified for the development of cyclodextrin polymers (branded as DEXSORB+) effective against a broad range of PFASs, that combines both electrostatic and hydrophobic interactions in a uniquely designed structure. In this Phase II application, we will continue our efforts to develop and optimize DEXSORB+ polymers with fast uptake kinetics and high adsorption capacities for PFASs and investigate and understand groundwater matrix effects systematically on PFAS adsorption performance and the ability to regenerate the adsorbent. We will also dedicate efforts to develop strategies for particle size control and then perform small-scale column testing in order to simulate a full-scale treatment process. These activities will provide us guidance on the operational conditions prior to moving onto pilot-scale studies.